Pancreatic regenerating protein I in chronic pancreatitis and aging: implications for new therapeutic approaches to diabetes.
OBJECTIVE
We investigated the relationship of pancreatic regenerating protein (reg) in models of acinar cell atrophy and aging, and the effect of reg I protein replacement on glucose tolerance.


METHODS
Rats underwent pancreatic duct ligation (PDL) and were followed through 12 months. Aging rats were studied at 12 and 20 months. Intraperitoneal glucose tolerance tests (IPGTTs) were performed, pancreatic reg I, reg I receptor, insulin gene expression, and reg I protein levels were measured. Pancreatic duct ligation and aged animals were treated with exogenous reg I protein and assessed for glucose metabolism.


RESULTS
After PDL, chronic atrophic pancreatitis developed, with a progressive loss of acinar cells and pancreatic reg I. During aging, a similar depression of reg I gene expression was also noted. The reg I levels correlated with pancreatic insulin levels. Twelve months after PDL, IPGTT results were abnormal, which were significantly improved by administration of reg I protein. Aged animals demonstrated depressed IPGTT, which marginally improved after reg I administration. Anti-reg antibody administration to young rats depressed IPGTT to elderly levels.


CONCLUSIONS
Depletion of the acinar product reg I is associated with the pathogenesis of impaired glucose tolerance of pancreatitis-associated diabetes and aging, and replacement therapy could be useful in these patients. Reg I is an acinar cell product, which affects islet function.
Bluth
Martin
M
Department of Surgery, SUNY Downstate Medical Center, Brooklyn, NY 11202, USA.
Mueller
Cathy M
CM
Pierre
Joelle
J
Callender
Gordon
G
Kandil
Emad
E
Viterbo
Domenico
D
Fu
Sophia L
SL
Sugawara
Akira
A
Okamoto
Hiroshi
H
Zenilman
Michael E
ME
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001284:Atrophy; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D008026:Ligation; D051847:Lithostathine / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010183:Pancreatic Ducts / Q000601:surgery; D050500:Pancreatitis, Chronic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage
D001786:Blood Glucose; D007328:Insulin; D051847:Lithostathine; C514404:REG I receptor, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C497616:Reg1a protein, rat